Vitamins, minerals, amino acids, co-enzymes and the like are compounds required by an animal or human body in varying amounts for the purposes of metabolism, biophysiological repair, immunity, growth, and cellular function and/or reproduction. These compounds also assist in the formation or control of hormones, blood cells, nervous-system chemicals, and genetic material.
Vitamins, minerals, amino acids, and co-enzymes are often referred to as nutrients, defined herein as a substance or ingredient which may be found in food which imparts a medicinal or health benefit. The various nutrient compounds are not chemically related, and most differ in their physiological actions. They generally act as catalysts, combining with proteins (or other biological substrates) to create metabolically active enzymes (or other biological components) that in turn produce hundreds of important chemical reactions and responses throughout an animal or human body. Without nutrients, many of these reactions would slow down or cease. The intricate ways in which nutrients act on the body, however, are still far from clear. The Food and Nutrition Board of the National Research Council replaced and expanded the Recommended Dietary Allowances (RDAs) with Dietary Reference Intakes (DRIs) to provide recommended vitamin, mineral, or other nutrient intakes for use in a variety of settings for humans.
The DRIs are actually a set of four reference values: Estimated Average Requirements (EAR), Recommended Dietary Allowances (RDA), Adequate Intakes (AI), and Tolerable Upper Intake Levels (UL). These values serve as recommended dosage levels for vitamins, minerals, or other nutrients. Currently there are no DRI's for intake of caffeine and other stimulants, or for L-glutamine or L-arginine. However, the U.S. National Library of Medicine and the National Institute of Health recommend, for example, that for caffeine, no more than 200 milligrams should be taken every three or four hours by an adult human, and that an adult human should not take more than 1600 mg in a twenty-four hour period. Additionally, L-arginine is typically provided in dietary supplements in dosages of about 100 milligrams, and L-glutamine in dosages of about 500 milligrams, pursuant to the guidelines of the United States Food & Drug Administration.
Pharmanutrients are generally referred to and described herein as a vitamin, mineral, amino acid, herb, botanical, or dietary substance which may be further delivered in some manner with or incorporated with a pharmacologically active ingredient for use to supplement an animal or human diet, treat an animal or human biological condition or disease state condition, or used to generate a biological response. Additionally, a pharmacologically active ingredient is generally referred to and described herein as any drug component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body of a human or animal. Thus, a pharmacologically active ingredient envisions not only prescription medications, but those that are considered non-prescription and/or over-the-counter (OTC) medications as well.
Dietary supplements are generally nutrient mixtures commonly taken in single standard and/or mega-dose dosage forms which contain vitamin, mineral and other nutrient doses equal to or over the Recommended Dietary Allowances (RDA) values. Although standard and/or mega-dose regimens are a common practice for the prevention of disease, there is a great deal of debate in the literature and medical community regarding the efficacy of such regimens. Moreover, consuming conventional large doses (i.e., standard or mega-dose) of vitamins, minerals, or other nutrients, in the absence of some deficiency and/or disease state, or without proper medical supervision, may cause harmful toxic effects and/or result in hypervitaminosis. The same can also be said of currently available pharmacologically active ingredients with or without conventional dosing and/or medical supervision with respect to the dosing regimens of those materials and their attendant side effect profiles.
Additionally, a consumer usually has little choice in choosing the variety of ingredients, dosage levels, or dosing regimens of a conventional dietary supplement or pharmanutrient product. Conventional dietary supplements, for example, tableted vitamins, may be effective for a general nutrient supplementation purpose, but usually provide an excess of vitamins, minerals, stimulants, or other ingredients which a consumer does not desire or require. Further, those same supplements may not adequately target an individual's specific dietary need or desired biological response at any given time. Moreover, conventional dosage forms of dietary supplements, nutrients, and pharmanutrients typically only allow a consumer to take one or two doses per any given twenty-four (24) hour period. As a result, conventional dietary supplements and pharmanutrients fail to recognize that the physiological state and resultant nutrient or pharmacologically active ingredient requirements of any single individual can depend upon and fluctuate based upon a number of different biophysical variables during the course of each day or dosing regimen period. For example, individual variations in diet as well as the amount and intensity of physical activity, provide physical and chemical stimuli that stress various systems of the body to differing degrees from one person to the next on any given day. Thus, conventional “one size fits all” nutrient, pharmanutrient, and individual pharmacological active ingredient mega-dose dosage forms/regimens are not amenable to empirical, individualized dosage adjustment to achieve an individualized biophysiological objective or response for various biological conditions or events.
Another drawback with most conventional dietary supplements, nutrients, or pharmanutrient product/systems is that they suffer from poor degrees and/or rates at which the various nutrients or active ingredients contained therein are absorbed into the systemic circulation of the human or animal body and made available for biophysiological activity (e.g., “bioavailability”). These degrees or rates of bioavailability typically depend upon the dose, dosage form, and method of administration of the various nutrients or active ingredients to the human or animal body.
One particular barrier to efficient nutrient or pharmacologically active ingredient bioavailability is “first-pass metabolism”, which is defined herein to mean a process in which the nutrient compound(s) or pharmacologically active ingredient(s) are modified, activated, or inactivated before they enter the systemic circulation, or is left unchanged and excreted. Alternatively, first-pass metabolism may be defined as the intestinal and hepatic degradation or alteration of a drug (i.e., pharmacologically active ingredient), nutrient, or other substance orally, and after absorption, removing some of the absorbed substance (i.e., active ingredient or nutrient) from the blood before it enters the general circulation to generate a biological response or effect.
For example, it is believed by some within the medical and dietary supplement communities that one significant drawback to “mega-dosing” of vitamins, minerals, other nutrients or pharmacologically active ingredients/drugs is that increased dosages may not be adequately absorbed into the human or animal body, or may actually decrease absorption. Thus, available transport mechanisms may become saturated and unable to absorb excess dose. Additionally, another drawback to vitamin, mineral, or drug delivery via a conventional tablet or capsule is that differences in luminal pH along the gastrointestinal tract lining, surface area per luminal volume, blood perfusion, presence of bile and mucus, and the nature of epithelial membranes may prevent efficient absorption, activation, and the like of a nutrient or drug, thereby decreasing the bioavailability of each. Additionally, as side effects are increased and/or the desired biological response, effect, or affect is decreased, individuals taking such conventional “mega-dose” supplements or pharmanutrients tend to become mal- or non-compliant. Thus, the current norm for temporal dynamics associated with such conventional therapies is lessened or prevented.
To compensate for first pass metabolism effects, some previous efforts have been directed to enterically coated tablets or capsular dosage forms which pass through the stomach unaltered to disintegrate in the lower intestines to attempt to achieve increased absorption of the nutrient or drug. However, aside from a delayed biophysiologic response as gastric emptying becomes rate-limiting, gastric irritability, and potential allergic reactions from the ingestion of such coating materials generally occur. Further, enterically coated delayed release dosage forms must dissolve and typically be absorbed within a narrow time frame. As a result, the human or animal body typically excretes the non-absorbed nutrient or drug rather than fully absorb and utilize either.
Additional previous attempts at minimizing first pass metabolism effects to increase the bioavailability of a nutrient or pharmacologically active ingredient have also been directed to continuous or gradual release dosage forms. U.S. Pat. No. 4,882,167, to Jang, discloses dry direct compressed products for controlled release of actives including vitamins or minerals. However, the compositions and methods of the Jang patent do not provide for ultra-low dosage amounts of vitamins or minerals, dosing flexibility, or a type of system, composition, or method for individualized, responsive dosing based on a desired and/or targeted biological response/effect/affect.
WO 99/17753 discloses rapidly dissolving films for delivery of drugs to be adsorbed in the digestive tract. U.S. Pat. No. 6,596,298, to Leung, discloses consumable oral care films which may optionally contain active amounts of pharmacologically active ingredients/drugs. However, these patents do not utilize vitamins or minerals, and more specifically, ultra-low dosage amounts of nutrients which would operate to provide flexibility for individualized dosing alone, or in conjunction or concert with, or in combination with a drug. Moreover, these products or processes do not provide a system or selection for varying the type or level of dosage depending on a biological response/effect/affect desired.
Therefore, there is presently a need for an efficient process for producing a pharmanutrient composition, dosing regimen and delivery system that is capable of individualized biologically responsive dosing (i.e., dosing based upon empirical analysis and adjustment), which is available in a suitable dosage form, and preferably is efficiently absorbed and made bioavailable to animal or human tissue. Additionally, there is presently a need for a treatment method for managing finely tuned biological needs and responses which utilizes ultra-low dosage amounts of nutrients, varied dosage amounts of a drug, substantially avoids first-pass metabolism, and allows for varied dosage/dosing regimens within each dosing period (e.g., 24 hours, 6 hours, 1 hour, 30 minutes, etc.).